PROJECT SUMMARY/ABSTRACT A seeming unrelenting opioid crisis is devastating the United States, with rural states and communities being hit especially hard. Actionable guidance is desperately needed to curb the death and devastation caused by opioid misuse and addiction. Recognizing the urgent need, the National Institute on Drug Abuse (NIDA) and the Substance Abuse and Mental Health Services Administration (SAMHSA) plan to launch the HEALing Communities Study (HEAL) to reduce opioid overdose fatalities by at least 40% in 3 years. Three research sites (RSs) and a data coordinating center (DCC) will be created to evaluate the implementation of evidence- based prevention and treatment interventions, and their cost and cost-effectiveness. RTI proposes to serve as the DCC for HEAL. In this capacity we will provide coordination and facilitate communications to unite the HEAL members into a cohesive research cooperative (Aim 1a). We will work with the RSs to apply implementation science methods to understand the barriers and facilitators to successful uptake of proven interventions in health care, behavioral care, criminal justice, and other public health settings (Aim 1b). Novel insights will be gained through the application of advanced data management, biostatistics, analytic, and computing techniques (Aim 2). We have the infrastructure in place to support rapid study start-up and efficient operations. Data harmonization will be enhanced using innovative methods and tools for selecting common data elements and for transforming data from many administrative systems to a consolidated HEAL data model. We will conduct health economics research to determine the incremental costs of start-up and ongoing implementation, and the cost-effectiveness of evidence-based approaches to mitigate the opioid epidemic (Aim 3). We will develop a microsimulation model that will inform optimal resource allocation to achieve target reductions in opioid overdose deaths and other negative outcomes. We will develop the Opioid Policy Simulator as a translational tool for communities (internal and external to HEAL) to use as they plan their own interventions to reduce opioid effects in their locales. The Simulator will be an interactive online tool to help decisionmakers synthesize information from multiple sources and select the combination of interventions best suited for their community. Our DCC team, led by multiple Principal Investigators Drs. Rick Williams, Gary Zarkin, and Kevin Conway are experienced leaders of multi-site studies and experts in data harmonization, biostatistics, health economics, and addiction etiology. Our broader team of investigators and consultants brings robust scientific and implementation science skills interwoven with a deep understanding of the opioid crisis.